The motile tips of embryonic axons integrate signaling information from a multitude of guidance molecules during development, plasticity, and regeneration following injury. The rodent taste system provides an especially attractive model in which to study these processes. A role for neurotrophic factors in guiding these afferents to their targets has been postulated. Several of these factors continue to be expressed in adult gustatory epithelium, consistent with the possibility that they have a role in maintaining the integrity and fidelity of interactions between afferents and their targets, particularly given that the targets undergo turnover. Our previous work showed that geniculate (taste) and trigeminal (somatosensory) ganglia dissected from embryos at different stages of development differ in their response to neurotrophic factors and guidance molecules. Whether geniculate axons change in their response to neurotrophic factors at postnatal and adult stages has not been studied. We intend to determine if geniculate and trigeminal ganglion neurites are promoted and attracted by neurotrophic factors in vitro, define the range of effective concentrations, and assess differences in the effects of these factors on ganglia dissected at different stages of embryonic and postnatal development. In addition, we will carry out analogous experiments using lingual gustatory epithelium, which expresses a subset of the neurotrophic factors that we will be studying. Hypotheses/Approaches: (Aim 1) We will test the hypothesis that BDNF is unique among neurotrophic factors in that it acts as an attractant for geniculate neurites at three embryonic, postnatal, and adult stages. Similarly we will determine if NT3, BDNF, and NGF, which are expressed in or near the target epithelium, are attractants for trigeminal axons. (Aim 2) We will test whether intact lingual taste bud-bearing epithelium or isolated and combined gustatory papillae are attractive to geniculate or trigeminal afferents. If they are attractive, we will assess the contribution of neurotrophic factors to that attraction. The primary approach will entail the culturing of ganglion explants in gels composed of collagen or mixtures of collagens, other extracellular matrix molecules, and growth factors. Co-culturing ganglia and slow-release beads soaked in the factor of interest or epithelium pieces will permit us to test if neurotrophic factors act directly on the neurites to guide them to their targets. The goal of this work is to gain an understanding of the role of neurotrophic factors in guiding axons to their targets during development and also in maintaining proper connections between nerves and their targets in adults. This knowledge will aid not only in understanding how the nervous system develops normally, but will enhance our understanding of what factors may be defective in disease and also which factors can be manipulated to improve the prospects for recovery from injury or disease. [unreadable] [unreadable]